1 / 32

Keith Dawkins MD FRCP FACC FSCAI Chief Medical Officer Senior Vice President

Why Boston Scientific Persists with the Two-Drug Strategy. Keith Dawkins MD FRCP FACC FSCAI Chief Medical Officer Senior Vice President Boston Scientific Corporation. London - January 2010. Conflicts of Interest. Employee Boston Scientific Corporation Stockholder

nimrod
Download Presentation

Keith Dawkins MD FRCP FACC FSCAI Chief Medical Officer Senior Vice President

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Why Boston Scientific Persists with the Two-Drug Strategy Keith Dawkins MD FRCP FACC FSCAI Chief Medical Officer Senior Vice President Boston Scientific Corporation London - January 2010

  2. Conflicts of Interest • Employee • Boston Scientific Corporation • Stockholder • Boston Scientific Corporation

  3. Boston Scientific Two-Drug Strategy TAXUS Liberté PROMUS

  4. Why do Interventional Cardiologists use a particular Stent? Marketing Cost Hospital Administrator Sales Safety Competition Competition Data Performance Hospitality Hospitality

  5. The TAXUS Program

  6. SPIRIT I SPIRIT II Everolimus SPIRIT III SPIRIT IV SPIRIT V PROMUS/XIENCE V

  7. TAXUS & SPIRIT: Follow-up (years) Years

  8. Prevalence of Diabetes Mellitus 1:3

  9. Which DES for the Diabetic Patient?

  10. SPIRIT IV: Primary Endpoint (TLF 1-yr) PSup=0.001 Target Lesion Failure (%) 101/2416 81/1195 TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLR 1 year = 365 ± 28 days

  11. SPIRIT IV: Impact of Diabetes (TLF 1-yr) XIENCE/PROMUS TAXUS Express P<0.001 P=0.80 Target Lesion Failure (%) 52/1652 55/815 49/761 26/379 TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLR 1 year = 365 ± 28 days

  12. SPIRIT IV: Impact of Diabetes Type (TLF 1-yr) XIENCE/PROMUS TAXUS Express P=0.64 P=0.83 Target Lesion Failure (%) 33/562 18/264 16/199 8/115 TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLR 1 year = 365 ± 28 days

  13. Diabetic Restenosis: the MAPK Pathway MEK ERK1/2 Advanced type II diabetes insulinreceptor insulin cell membrane InsulinResistance MAPK Pathway PI3K Pathway IRS1/2 mTOR Paclitaxel P70 S6K • cell migration • cell proliferation MEK - MAPK/ERK kinase ERK – extracellular signal-related kinase Promotes Restenosis ArteriosclerThrombVascBiol 2006;26:1473-1480

  14. TAXUS Trials & Registries (TLR)Diabetic*vs.non-Diabetic, TAXUS-treated patients Sample Size OddsRatio LowerLimit UpperLimit RelativeWeight Study DM NoDM Odds Ratio and 95% CI TAXUS II 22 238 0.275 0.016 4.722 0.57 SPIRIT III 92 238 0.430 0.152 1.218 4.22 TAXUS V 183 394 0.843 0.520 1.367 19.56 SPIRIT IV 399 829 1.047 0.593 1.847 14.18 TAXUS VI MR 39 180 1.105 0.427 2.859 5.07 ATLAS SV 56 191 1.152 0.231 5.761 1.77 ATLAS DS 95 165 1.172 0.495 2.773 6.17 SIRTAX 93 416 1.523 0.824 2.816 12.12 TAXUS IV 155 507 1.725 0.982 3.033 14.39 ATLAS WH 220 650 1.918 1.166 3.155 18.48 ATLAS LL 42 108 3.467 1.102 10.907 3.48 1396 3916 1.272 1.027 1.576 TRIALS: Ontario 835 1219 1.033 0.772 1.383 16.98 ARRIVE 2 1437 3568 1.043 0.830 1.310 27.65 ARRIVE 1 675 1812 1.082 0.787 1.487 14.22 OLYMPIA III 3160 9287 1.103 0.878 1.387 27.52 OLYMPIA II 2711 6523 1.113 0.804 1.541 13.63 REGISTRIES: 8818 22409 1.073 0.951 1.209 Combined Estimate: 10214 26325 1.117 1.006 1.241 Favours Diabetes Favours No Diabetes 11% Relative Increase in TLR for Patients with Diabetes Published Data up to 01.2010 *Medically Treated Diabetes

  15. -Olimus Trials & Registries (TLR)Diabetic vs. Non-Diabetic, -Olimus-treated patients Sample Size OddsRatio LowerLimit UpperLimit RelativeWeight Study DM NoDM Odds Ratio and 95% CI SIRTAX 108 395 0.932 0.415 2.090 9.13 SPIRIT III 198 471 0.942 0.449 1.979 10.82 ENDEAVOR I-III 293 1004 1.308 0.779 2.196 22.18 SIRIUS 131 402 1.826 0.987 3.376 15.77 SPIRIT IV 786 1669 2.392 1.448 3.950 23.67 ARTS II 159 448 2.668 1.496 4.758 17.79 PORTO I & II 114 150 6.519 0.308 138.015 0.64 1789 4539 1.707 1.337 2.179 TRIALS: * * ELISIR 582 1605 1.244 0.862 1.797 12.87 * * German CYPHER 1948 4707 1.252 1.042 1.505 51.57 * Ontario Registry 835 1219 1.607 1.205 2.144 20.98 Berenguer, 2006 98 133 1.645 0.488 5.539 1.18 EVASTENT 844 887 1.804 1.130 2.881 7.94 Kumar, 2007 297 541 2.894 1.587 5.277 4.82 Hoffman, 2007 71 226 8.288 1.585 43.343 0.64 4675 9318 1.435 1.258 1.637 REGISTRIES: Combined Estimate: 6464 13857 1.492 1.329 1.676 Favours Diabetes Favours Non-Diabetes 49% Relative Increase in TLR for Patients with Diabetes *TLR not reported; TVR rates were used. Published Data up to 01.2010

  16. TAXUS IV: 5-yr Clinical Results TAXUS Express BMS Patients (%) Diabetes n=163 No Diabetes n=480 Diabetes n=152 No Diabetes n=499 J Am Coll Cardiol Intv 2009;2:1248-1259

  17. Late Loss drift… 6 Months 2-5 Years …is it clinically important?

  18. SPIRIT II: In-Stent Late Loss 6 months vs. 2 Years 2 Years 6 Months 100 100 Xience/Promus TAXUS Xience/Promus TAXUS 80 80 + * 60 60 % of Lesions 40 40 20 20 0 0 -0.75 -0.5 -0.25 0 0.25 0.5 0.75 1 1.25 1.5 1.75 2 -0.75 -0.5 -0.25 0 0.25 0.5 0.75 1 1.25 1.5 1.75 2 In-stent Late Loss (mm) In-stent Late Loss (mm) Xience/Promus: 0.33 ± 0.37 (n=97) TAXUS: 0.34 ± 0.34 (n=35) P=0.6026 Xience/Promus: 0.17 ± 0.32 (n=97) TAXUS: 0.33 ± 0.32 (n=35) P=0.0037

  19. SIRTAX: 8 months vs. 5 years QCA follow-up P5years=0.21 P8months<0.001 In-Stent Late Loss (mm) Δ 0.12mm Δ 0.18mm

  20. SIRTAX: Clinical MACE 5 Years follow-up

  21. TAXUS II: Late Loss Stability over Time P=0.1669 In-Stent Late Loss (mm) Am J Cardiol 2007;99:607-615

  22. Is the BSC Two-Drug Strategy Working? 45% 46% 48% DES Market Share (%) Source: MRG, BSJ, BSC Internal Data (December 2009)

  23. Element Stent Platform Geometry designed for drug delivery Four stent models Consistent surface-to-artery ratios Apex™ balloon Bi-component balloon Multilayer Platinum Chromium Alloy Thin struts Radio-opaque Low recoil High radial strength Cypher 0.0055” Express 0.0052” Liberté 0.0038” Element 0.0032” Vision 0.0032” Driver 0.0036”

  24. BSC Two Drug Strategy Paclitaxel Everolimus Element Stent Element Stent Trial Complete N=1488 Trial Complete N=1828

  25. BSC Two Drug Strategy Paclitaxel Everolimus Element Stent Direct Drug comparison on the same ELEMENT Platform

  26. Next Generation DES Attributes • Safety • No Stent Thrombosis (‘BMS’ like) • Shortened/No DAPT Requirement • Efficacy • Low Late Loss, Binary Restenosis • Low TLR, Low Clinical Symptom Recurrence

  27. Lowering the Requirement for DAPT? Reduced Polymer Load Ablumenal Polymer Bioerodable Polymer No Polymer Reduced Drug Load Stent Delivery System Stent Material Thinner Struts Modified Stent Geometry Surface Coating

  28. JACTAX HD Results vs. ATLAS Matched (9 months) p=0.17 p=0.23 Late Loss (mm) Labcoat Liberté (n=97) Taxus Liberté (n=215) Taxus Liberté (n=215) Labcoat Liberté (n=97) In-Stent In-Segment J Am Coll Cardiol Intv 2010. In Press

  29. Labcoat Relative Polymer Thickness Micron (µ) LABCOAT Polymer (Thickness) E. Coli (Length) Red Cell (Diameter) T. Liberté Polymer (Thickness) Neutrophil (Diameter) LABCOAT = Minimal Drug + Ultrathin Bioerodable Abluminal Polymer

  30. Relative Drug Coating Weights Bare Metal Nevo T. Liberté BioMatrix Jactax HD Promus Jactax LD 10µg 20µg // // // l l l l l l l l l l l 0 50 100 150 200 250 300 350 500 685 1267 Coating Weight (µg, 16mm Stent)

  31. BSC Two Drug Strategy Everolimus Paclitaxel Next Generation DES Low Drug Dose, Ablumenal Delivery, Bioerodable Polymer Short DAPT ? Labcoat Element Labcoat Liberté EVOLUTION Trial Complete N=103 Trial to commence Q2 2010

  32. Conclusions: Nine years of clinical data attest to the safety and efficacy of TAXUS stents. Differences in outcome between Diabetic and Non-Diabetic patients based on the MOA is real, favouring Paclitaxel as the drug of choice. Late Loss drift associated with –olimus eluting stents remains an unresolved issue of possible clinical significance. The Two-Drug strategy affords dominant market share. BSC continues to assess the roles of a Two-Drug strategy in the DES pipeline.

More Related